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Reduction of Alveolar Epithelial Ion and Fluid Transport by Inflammatory Mediators

University of California, San Francisco, California

Hans G. Folkesson, Ph.D.

Northeastern Ohio University, Rootstown, Ohio

From the Authors:

We appreciate Dr. Eisenhut's thoughtful comments on the contribution of inflammatory mediators in regulating alveolar epithelial ion and fluid transport, thus influencing the rate at which alveolar edema is resolved in acute lung injury. We believe that some caution should be exercised in the interpretation of studies in which nasal airway potential difference is used to estimate the effect of pathologic conditions (such as meningococcal septicemia) on alveolar epithelial ion and fluid transport. In addition, as Dr. Eisenhut explains, TNF- has been shown to up-regulate alveolar fluid clearance under some pathologic conditions (1–3), while under other conditions TNF- seems to decrease alveolar fluid clearance (4). Thus, the net effect under pathologic conditions is not clear. We have also reported that IL-1 can decrease alveolar epithelial ion transport (5). The net effect of NO on alveolar epithelial fluid clearance is not entirely clear based on the available data. Some studies show an inhibitory effect on alveolar fluid clearance (6, 7), but the net effect under pathologic conditions deserves further study. There is also evidence that TGF- can down-regulate alveolar fluid transport (8). We do agree that reduction and expression and function of CFTR may be an important mechanism for down-regulating alveolar fluid clearance under pathologic conditions (9). Finally, the potential role of ₂-agonist therapy in reducing extravascular lung water could include both modest anti-inflammatory effects and the capacity to up-regulate the rate of alveolar fluid clearance (10). Again, we appreciate Dr. Eisenhut's thoughtful comments about the potential effect of inflammatory mediators on alveolar fluid transport under pathologic conditions.

Footnotes

Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

References

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